Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.
复制标题
靶向cGAS-STING信号传导在神经系统疾病中的机制和治疗潜力。
DOI：
10.1186/s13024-023-00672-x
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发表时间：
2023-11-08
影响因子：
15.1
通讯作者：
Gan L
中科院分区：
文献类型：
--
作者：
Huang Y;Liu B;Sinha SC;Amin S;Gan L
DNA传感是先天免疫系统的关键组成部分，负责检测错误定位的DNA并触发下游炎症途径。在DNA传感器中，环GMP-AMP合成酶（cGAS）是检测细胞质DNA的主要参与者，包括来自病原体的外源DNA和细胞损伤过程中释放的自身DNA，最终通过干扰素基因激活刺激物（STING）激活I型干扰素（IFN-I）反应。IFN-I细胞因子在介导神经炎症中是必不可少的，这在中枢神经系统损伤、神经退行性变和衰老中被广泛观察到，这表明cGAS DNA传感通路在上游发挥作用。本文综述了cGAS-STING dna驱动免疫反应在各种神经系统疾病和病症中的最新进展。我们的综述涵盖了目前对cGAS激活的分子机制的理解，并重点介绍了cGAS- sting信号在中枢和周围神经系统中的各种细胞类型，如常驻脑免疫细胞、神经元和胶质细胞。然后，我们讨论了cGAS-STING信号在不同神经退行性疾病中的作用，包括牛头病、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症，以及衰老和衰老。最后，我们列出了目前cGAS抑制剂的研究和开发进展，并评估了靶向cGAS和STING作为广泛神经系统疾病治疗策略的前景。
DNA sensing is a pivotal component of the innate immune system that is responsible for detecting mislocalized DNA and triggering downstream inflammatory pathways. Among the DNA sensors, cyclic GMP-AMP synthase (cGAS) is a primary player in detecting cytosolic DNA, including foreign DNA from pathogens and self-DNA released during cellular damage, culminating in a type I interferon (IFN-I) response through stimulator of interferon genes (STING) activation. IFN-I cytokines are essential in mediating neuroinflammation, which is widely observed in CNS injury, neurodegeneration, and aging, suggesting an upstream role for the cGAS DNA sensing pathway. In this review, we summarize the latest developments on the cGAS-STING DNA-driven immune response in various neurological diseases and conditions. Our review covers the current understanding of the molecular mechanisms of cGAS activation and highlights cGAS-STING signaling in various cell types of central and peripheral nervous systems, such as resident brain immune cells, neurons, and glial cells. We then discuss the role of cGAS-STING signaling in different neurodegenerative conditions, including tauopathies, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as aging and senescence. Finally, we lay out the current advancements in research and development of cGAS inhibitors and assess the prospects of targeting cGAS and STING as therapeutic strategies for a wide spectrum of neurological diseases.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
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作者：
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通讯作者：
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影响因子：
4.3
作者：
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通讯作者：
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DOI：
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发表时间：
2019-03-12
影响因子：
11.1
作者：
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通讯作者：
Silverman, Robert H.
影响因子：
5.2
作者：
Lu, Zengzeng;Fu, Yuqian;Zhou, Xueyuan;Du, Hekang;Chen, Qi
通讯作者：
Chen, Qi
DOI：
10.1126/science.1252945
发表时间：
2014-10-03
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Schwartz M